Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor.
Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor.
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DOI：
10.1099/mic.0.036475-0
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Maiden MCJ
中科院分区：
文献类型：
--
作者：
Evans NJ;Harrison OB;Clow K;Derrick JP;Feavers IM;Maiden MCJ
由血清群B脑膜炎奈瑟菌引起的脑膜炎球菌病在世界许多地方仍然是一个重要的健康问题，目前没有全面的疫苗。免疫原性差，加上对人唾液酸的免疫学特性，阻碍了血清群B缀合物疫苗的开发，导致替代疫苗候选物的开发，包括许多基于外膜蛋白（OMP）的制剂。然而，基于蛋白质的脑膜炎球菌疫苗的设计由于脑膜炎球菌的高水平遗传和抗原多样性而变得复杂。这种多样性的程度和结构的知识可能对使用特定蛋白质作为潜在的疫苗候选物具有影响。考虑到这一点，研究了脑膜炎球菌OMP HmbR在N.脑膜炎分离株代表主要的高度侵袭性谱系。与其他脑膜炎球菌抗原一样，hmbR的遗传多样性来自种内水平遗传交换和从头突变的组合。此外，系谱分析显示hmbR基因与克隆复合体相关，并出现两个hmbR家族，A和B。三个可变区（VR 1-VR 3），位于环2，3和4，观察与VR型的克隆复合体结构。少数密码子（3.9%）位于2D模型的假定表面暴露环区域内，处于多样化选择下，表明蛋白质的区域可能受到免疫攻击。
Meningococcal disease caused by serogroup B Neisseria meningitidis remains an important health problem in many parts of the world, and there are currently no comprehensive vaccines. Poor immunogenicity, combined with immunological identity to human sialic acids, have hindered the development of a serogroup B conjugate vaccine, resulting in the development of alternative vaccine candidates, including many outer-membrane protein (OMP)-based formulations. However, the design of protein-based meningococcal vaccines is complicated by the high level of genetic and antigenic diversity of the meningococcus. Knowledge of the extent and structuring of this diversity can have implications for the use of particular proteins as potential vaccine candidates. With this in mind, the diversity of the meningococcal OMP HmbR was investigated among N. meningitidis isolates representative of major hyper-invasive lineages. In common with other meningococcal antigens, the genetic diversity of hmbR resulted from a combination of intraspecies horizontal genetic exchange and de novo mutation. Furthermore, genealogical analysis showed an association of hmbR genes with clonal complexes and the occurrence of two hmbR families, A and B. Three variable regions (VR1–VR3), located in loops 2, 3 and 4, were observed with clonal complex structuring of VR types. A minority of codons (3.9 %), located within putative surface-exposed loop regions of a 2D model, were under diversifying selection, indicating regions of the protein likely to be subject to immune attack.
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影响因子：
3.3
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